The marriage of cancer vaccines and antiangiogenesis
9/2/2005 Besthesda, MD Jeffrey Schlom Blood, 15 September 2005, Vol. 106, No. 6, pp. 1897-1898 An innovative approach to the use of cancer vaccines targets the vascular endothelial growth factor receptor-2 (FLK-1), suppresses tumor-associated angiogenesis, and results in antitumor activity. In a highly innovative approach to the suppression of tumor growth, Zhou and colleagues (a) have developed an anticancer vaccine that targets the vascular endothelial growth factor receptor-2 (VEGF-R2, FLK-1), an important molecule expressed on tumor-associated endothelial cells.(1) Angiogenesis is a rate-limiting step in the development of tumors of any appreciable size.(2) Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases have been shown to play important roles in angiogenesis. VEGF-R2, also known as FLK-1, demonstrates expression restricted to endothelial cells and is up-regulated once these cells proliferate during angiogenesis in the tumor vasculature. Numerous approaches by many groups have been used to block FLK-1, including the use of monoclonal antibodies against VEGF and the use of synthetic receptor kinase inhibitors. In this issue of Blood, Zhou and colleagues demonstrate the broad depth to which vaccines can be used to attack tumors. Previous studies by this group have demonstrated that vaccines containing the entire FLK1 gene can suppress tumor growth.(3) In the study reported here, however, they used an oral DNA minigene vaccine, using a Salmonella-based vector containing only a single cytotoxic T lymphocyte (CTL) epitope of FLK-1. The oral carrier system, consisting of a double attenuated strain of Salmonella typhimurium, delivers the DNA to secondary lymphoid organs for [...]